ANN ARBOR—Immunity to whooping cough lasts at least 30 years on average, much longer than previously thought, an analysis by researchers at the University of Michigan and the University of New Mexico shows.

The research, by U-M professor of ecology and evolutionary biology Pejman Rohani and his former postdoctoral fellow Helen Wearing, who is now an assistant professor at the University of New Mexico, is scheduled to be published Oct. 23 in the open-access journal PLoS Pathogens.

Once thought to be under control, thanks to widespread childhood vaccination, whooping cough (pertussis) has been on the rise since the 1980s in the United States and several other countries. This increase has fueled concerns about the effectiveness of current vaccination practices and raised the question of whether whooping cough can ever be eradicated.

Several explanations have been proposed for the surprising increase in cases, and one leading idea is that the immunity enjoyed by vaccinated or previously exposed people is simply wearing off. It’s been documented that in some individuals immunity has waned over time, but the exact details of how long protection typically lasts and how its waning affects disease transmission have not been clear.

One way of exploring those questions would be to follow a group of people over time, tracking changes in their immune status. But that would be a large-scale, long-term undertaking, made all the more difficult by the fact that no clear-cut blood test exists for determining protection against pertussis infection.

Rohani and Wearing took a different approach, using mathematical models to explore various scenarios and comparing the predictions generated by those models to data on whooping cough incidence.

The researchers constructed two models with different assumptions about what happens when a person whose immunity has lapsed is exposed to pertussis and how much that person contributes to transmission. Then they compared the models’ predictions to whooping cough incidence data from England and Wales from both the pre-vaccine era (1945-1957) and the vaccine era (1958-1972). In particular, Rohani and Wearing looked for matches in two key measures: the number of years between big outbreaks and the frequency of “extinctions”, periods of time when no whooping cough cases were reported in the population.

The analysis revealed that, on average, whooping cough immunity lasts at least 30 years and perhaps as long as 70 years after natural infection. “This is surprising because clinical epidemiologists currently believe the duration of pertussis immunity is somewhere between four and 20 years,” said Rohani, who also has an appointment in the Center for the Study of Complex Systems.

In addition, repeat infections appear to contribute relatively little to the transmission cycle, the researchers found. And when people whose immunity has waned are re-exposed to whooping cough, they rarely become infected. In fact, their immunity to the disease may be boosted by re-exposure, the study suggests.

If correct, the results represent encouraging news, Rohani said. “They suggest that loss of immunity may be playing a less significant role than is currently thought. And at least in these historical data, vaccination seems to interrupt transmission substantially.”

Still, the researchers are cautious about drawing conclusions about current day vaccination practices from their study of historical data. “It’s worth pointing out that in the past 20 years or so, the nature of the vaccines that have been used has changed quite fundamentally,” Rohani said. “The data we’re using are from a time when a whole-cell vaccine was in use; now an acellular vaccine, which stimulates a different part of the immune system, is typically used, especially in North America.”

In new work, Rohani is using more recent data from the U.S., trying to uncover relevant factors associated with trends in whooping cough incidence.

“In the U.S. data, there’s a significant amount of variation among states,” he said. “Some states show a strong resurgence in whooping cough, some show a decline, and some show no change. We’re looking at demographic variables like birth rates, and immigration profiles, population size and vaccination coverage, to see if we can discover key predictors.”

In addition, Rohani is examining the historic data used in the PLoS Pathogens paper with different statistical methods, as well as developing models that incorporate explicit immunological information. Another project involves analyzing pertussis incidence data from Senegal, where detailed information on individuals’ vaccination, infection and reinfection histories has been kept on a population of 30,000 people.

“These are all ongoing and complementary studies,” Rohani said, “that will shed further light on this important, but enigmatic infectious disease.”

The researchers received funding from the National Institutes of Health; the RAPIDD program of the Science & Technology Directorate, Department of Homeland Security; and the Gates Foundation.

Related Links:

• PLoS Pathogens